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heparin

 

Classes: Anticoagulants, Cardiovascular; Anticoagulants, Hematologic

Dosing and uses of Heparin

 

Adult dosage forms and strengths

heparin lock solution

  • 10units/mL
  • 100units/mL

injectable solution

  • 1000units/mL
  • 2500units/mL
  • 5000units/mL
  • 10,000units/mL
  • 20,000units/mL

premixed IV solution

  • 20,000units/500mL
  • 25,000units/250mL
  • 25,000units/500mL

 

DVT & PE

Prophylaxis

  • 5000 units SC q8-12hr, OR
  • 7500 units SC q12hr

Treatment

  • 80 units/kg IV bolus, THEN continuous infusion of 18 units/kg/hr, OR
  • 5000 units IV bolus, THEN continuous infusion of 1300 units/hr, OR
  • 250 units/kg (alternatively, 17,500 units) SC, THEN 250 units/kg q12hr

Dosing considerations

  • Numerous concentrations available; extreme caution is required to avoid medication error

 

Acute Coronary Syndromes

PCI

  • Without GPIIb/IIIa inhibitor: Initial IV bolus of 70-100 units/kg (target ACT 250-300 sec)
  • With GPIIb/IIIa inhibitor: Initial IV bolus of 50-70 units/kg (target ACT >200 sec)

STEMI

  • Patient on fibrinolytics: IV bolus of 60 units/kg (max: 4000 units), THEN 12 units/kg/hr (max 1000 units/hr) as continuous IV infusion
  • Dose should be adjusted to maintain aPTT of 50-70 sec

Unstable Angina/NSTEMI

  • Initial IV bolus of 60-70 units/kg (max: 5000 units), THEN initial IV infusion of 12-15 units/kg/hr (max: 1000 units/hr)
  • Dose should be adjusted to maintain aPTT of 50-70 sec

Dosing considerations

  • Numerous concentrations available; extreme caution is required to avoid medication error

 

Anticoagulation

Intermittent IV injection

  • 8000-10,000 units IV initially, THEN 50-70 units/kg (5000-10,000 units) q4-6hr

Continuous IV infusion

  • 5000 units IV injection, followed by continuous IV infusion of 20,000-40,000 units/24 hr

Dosing considerations

  • Numerous concentrations available; extreme caution is required to avoid medication error

 

Catheter Patency

Prevention of clot formation within venous and arterial catheters

Use 100 units/mL; instill enough volume to fill lumen of catheter

Dosing considerations

  • Numerous concentrations available; extreme caution is required to avoid medication error
  • Amount and frequency depends on catheter volume and type
  • Peripheral heparin locks typically are flushed q6-8hr

 

Dosing Modifications

Hepatic impairment: Caution is advised; dosage adjustment may be required

 

Pediatric dosage forms and strengths

heparin lock solution

  • 10units/mL
  • 100units/mL

injectable solution

  • 1000units/mL
  • 5000units/mL
  • 10,000units/mL

 

Venous Thromboembolic Prophylaxis (Off-label)

100-150 units/kg IV once

 

Venous Thromboembolic Treatment (Off-label)

<1 year

  • Loading dose of 75 units/kg IV, THEN 28 units/kg/hr IV as initial maintenance dose

>1 year

  • Loading dose of 75 units/kg IV, THEN 20 units/kg/hr IV as initial maintenance dose

Intermittent IV injection

  • Initially give 50-100 units/kg IV infusion, THEN 100 units/kg IV infusion q4hr as a maintenance dose

 

Catheter Patency (Off-label)

Initially give 50-100 units/kg IV infusion, THEN 100 units/kg IV infusion q4hr as maintenance dose

Infants under 10 kg: 10 units/mL; instill enough volume to fill lumen of catheter

Children and infants over 10 kg: 10-100 units/mL; instill enough volume to fill lumen of catheter

 

Dosing Considerations

Numerous concentrations available; extreme caution is required to avoid medication error

There are no adequate, well-controlled studies on heparin use in pediatric patients; pediatric dosing recommendations are based on clinical experience

Use preservative-free heparin in neonates and infants; benzyl alcohol preservative has been associated with serious adverse effects (ie, gasping syndrome, which is characterized by central nervous system depression, metabolic acidosis, and gasping respirations) and death in pediatric patients

Venous thromboembolic treatment (off-label)

  • Adjust heparin dose based on desired aPTT

Catheter patency (off-label)

  • Dosage amount and frequency depend on catheter volume and type
  • Peripheral heparin locks typically are flushed q6-8hr

 

Heparin adverse (side) effects

>10%

Heparin-induced thrombocytopenia, possibly delayed (10-30% )

 

Frequency not defined

Mild pain

Hematoma

Hemorrhage

Local irritation

Erythema

Injection site ulcer (after deep SC injection)

Increased liver aminotransferase

Anaphylaxis

Immune hypersensitivity reaction

Osteoporosis (long-term, high-dose use)

 

Warnings

Contraindications

History of heparin-induced thrombocytopenia (HIT) (with or without thrombosis)

Uncontrolled, active bleeding (except DIC)

Conditions in which coagulation tests cannot be performed at appropriate intervals

 

Cautions

Any risk factor for hemorrhage (eg, subacute bacterial endocarditis, blood dyscrasias, menorrhagia, dissecting aneurysm, major surgery, spinal anesthesia, hemophilia, GI ulcerative lesions, liver disease, impaired hemostasis)

Heparin-induced thrombocytopenia may occur (with or without thrombosis) including thrombus formation on a prosthetic cardiac valve; immune-mediated reaction resulting from irreversible aggregation of platelets; monitor thrombocytopenia of any degree; if platelet count falls below 100,000/m³, discontinue anticoagulants

Monitor therapy with aPTt

Heparin may prolong Pt

History of allergy

Potential medication errors: Do not use heparin sodium injection as a catheter lock-flush product; heparin sodium injection is supplied in vials containing various strengths of heparin; these include vials containing a highly concentrated solution of 10,000 units in 1 mL, which have been mistaken for 1 mL low-concentration catheter lock-flush vials

Geriatric dosing: Lower doses may be necessary; patients over 60 years may have enhanced serum levels and response compared with patients under 60 years receiving similar dosages

If preserved with benzyl alcohol, do not administer to neonates, infants, pregnant women, or breastfeeding women; benzyl alcohol has been associated with serious adverse events and death, particularly in pediatric patients (gasping syndrome)

Blood coagulation tests guide therapy for full-dose heparin; monitor platelet count and hematocrit in all patients receiving heparin

 

Pregnancy and lactation

Pregnancy category: C

Lactation: Not excreted in breast milk; compatible

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of Heparin

Mechanism of action

Mechanism for low dose: Inactivates factor Xa and inhibits conversion of prothrombin to thrombin

Mechanism for high dose: Inactivates factors IX, X, XI, and XII and thrombin and inhibits conversion of fibrinogen to fibrin

Also inhibits activation of factor VIII

 

Absorption

Bioavailability: 22-40%

Onset: IV (immediate); SC (20-30 min)

Peak plasma time: 2-4 hr

 

Distribution

Protein bound: Extensive

 

Metabolism

Metabolized in the liver (partial) and reticuloendothelial system (partial)

Metabolites: None

 

Elimination

Half-life: 60-90 min average (longer at higher doses)

Dialyzable: No

Excretion: Urine

 

Administration

IV Incompatibilities

Additive

  • Dobutamine
  • Erythromycin
  • Gentamicin
  • Haloperidol
  • Hydrocortisone
  • Meperidine
  • Morphine
  • Vancomycin

Syringe

  • Amiodarone
  • Diazepam
  • Erythromycin
  • Gentamicin
  • Haloperidol
  • Meperidine
  • Morphine(?)
  • Vancomycin

Y-site

  • Amiodarone
  • Diazepam
  • Dobutamine
  • Gentamicin
  • Haloperidol
  • Vancomycin

Not spec

  • Hydroxyzine
  • Tetracycline

 

IV Compatibilities

Additive

  • Aminophylline
  • Ampho B
  • Ampicillin
  • Ca gluconate
  • Clindamycin
  • Dopamine
  • Esmolol
  • Furosemide
  • Lidocaine
  • Norepinephrine
  • KCl
  • Na bicarbonate
  • Verapamil
  • Vitamins B/C

Syringe

  • Aminophylline
  • Ampho B
  • Ampicillin
  • Atropine
  • Cimetidine
  • Clindamycin
  • Dobutamine
  • Dopamine
  • Epinephrine
  • Furosemide
  • Lidocaine
  • Morphine(?)
  • Norepinephrine
  • Na bicarbonate
  • Verapamil

Y-site

  • Aminophylline, ampicillin, atropine, Ca gluconate, cimetidine, clindamycin, dopamine, epinephrine, erythromycin, esmolol, furosemide, hydrocortisone, lidocaine, norepinephrine, meperidine, morphine, KCl, Na bicarbonate

 

IV Preparation

Recommended infusion concentration for most patients is 25,000 units in 500 mL D5W (50 units/mL premixed infusion solution)

 

IV Administration

IV injection may be given undiluted or diluted in 50-100 mL NS or D5W

Infusion: Dilute in NS, D5W, or other compatible fluid

Continuous IV therapy is preferred because intermittent IV therapy produces a higher incidence of bleeding abnormalities

Invert IV bag at least 6 times to ensure mixing and prevent pooling of medication

Use constant-rate IV infusion pump

 

Storage

Store heparin solutions at room temperature; do not freeze

Do not use if discolored/precipitates

Autoclavable